Parenteral nutrition emulsion inhibits CYP3A4 in an iPSC derived liver organoids testing platform.

OBJECTIVES: Parenteral nutrition (PN) is used for patients of varying ages with intestinal failure to supplement calories. Premature newborns with low birth weight are at a high risk for developing PN associated liver disease (PNALD) including steatosis, cholestasis, and gallbladder sludge/stones. To optimize nutrition regimens, models are required to predict PNALD. METHODS: We have exploited induced pluripotent stem cell derived liver organoids to provide a testing platform for PNALD. Liver organoids mimic the developing liver and contain the different hepatic cell types. The organoids have an early postnatal maturity making them a suitable model for premature newborns. To mimic PN treatment we used medium supplemented with either clinoleic (80% olive oil/20% soybean oil) or intralipid (100% soybean oil) for 7 days. RESULTS: Homogenous HNF4a staining was found in all organoids and PN treatments caused accumulation of lipids in hepatocytes. Organoids exhibited a dose dependent decrease in CYP3A4 activity and expression of hepatocyte functional genes. The lipid emulsions did not affect overall organoid viability and glucose levels had no contributory effect to the observed results. CONCLUSIONS: Liver organoids could be utilized as a potential screening platform for the development of new, less hepatotoxic PN solutions. Both lipid treatments caused hepatic lipid accumulation, a significant decrease in CYP3A4 activity and a decrease in the RNA levels of both CYP3A4 and CYP1A2 in a dose dependent manner. The presence of high glucose had no additive effect, while Clinoleic at high dose, caused significant upregulation of interleukin 6 and TLR4 expression.

Brain fatty acid and transcriptome profiles of pig fed diets with different levels of soybean oil.

BACKGROUND: The high similarity in anatomical and neurophysiological processes between pigs and humans make pigs an excellent model for metabolic diseases and neurological disorders. Lipids are essential for brain structure and function, and the polyunsaturated fatty acids (PUFA) have anti-inflammatory and positive effects against cognitive dysfunction in neurodegenerative diseases. Nutrigenomics studies involving pigs and fatty acids (FA) may help us in better understanding important biological processes. In this study, the main goal was to evaluate the effect of different levels of dietary soybean oil on the lipid profile and transcriptome in pigs' brain tissue. RESULTS: Thirty-six male Large White pigs were used in a 98-day study using two experimental diets corn-soybean meal diet containing 1.5% soybean oil (SOY1.5) and corn-soybean meal diet containing 3.0% soybean oil (SOY3.0). No differences were found for the brain total lipid content and FA profile between the different levels of soybean oil. For differential expression analysis, using the DESeq2 statistical package, a total of 34 differentially expressed genes (DEG, FDR-corrected p-value < 0.05) were identified. Of these 34 DEG, 25 are known-genes, of which 11 were up-regulated (log2 fold change ranging from + 0.25 to + 2.93) and 14 were down-regulated (log2 fold change ranging from - 3.43 to -0.36) for the SOY1.5 group compared to SOY3.0. For the functional enrichment analysis performed using MetaCore with the 34 DEG, four pathway maps were identified (p-value < 0.05), related to the ALOX15B (log2 fold change - 1.489), CALB1 (log2 fold change - 3.431) and CAST (log2 fold change + 0.421) genes. A "calcium transport" network (p-value = 2.303e-2), related to the CAST and CALB1 genes, was also identified. CONCLUSION: The results found in this study contribute to understanding the pathways and networks associated with processes involved in intracellular calcium, lipid metabolism, and oxidative processes in the brain tissue. Moreover, these results may help a better comprehension of the modulating effects of soybean oil and its FA composition on processes and diseases affecting the brain tissue.

Lipid Emulsion Inhibits Amlodipine-Induced Nitric Oxide-Mediated Vasodilation in Isolated Rat Aorta.

This study aimed to examine the effect of lipid emulsion on the vasodilation induced by a toxic dose of amlodipine in isolated rat aorta and elucidate its mechanism, with a particular focus on nitric oxide. The effects of endothelial denudation, NW-nitro-L-arginvine methyl ester (L-NAME), methylene blue, lipid emulsion, and linolenic acid on the amlodipine-induced vasodilation and amlodipine-induced cyclic guanosine monophosphate (cGMP) production were examined. Furthermore, the effects of lipid emulsion, amlodipine, and PP2, either alone or combined, on endothelial nitric oxide synthase (eNOS), caveolin-1, and Src-kinase phosphorylation were examined. Amlodipine-induced vasodilation was higher in endothelium-intact aorta than in endothelium-denuded aorta. L-NAME, methylene blue, lipid emulsion, and linolenic acid inhibited amlodipine-induced vasodilation and amlodipine-induced cGMP production in the endothelium-intact aorta. Lipid emulsion reversed the increased stimulatory eNOS (Ser1177) phosphorylation and decreased inhibitory eNOS (Thr495) phosphorylation induced via amlodipine. PP2 inhibited stimulatory eNOS, caveolin-1, and Src-kinase phosphorylation induced via amlodipine. Lipid emulsion inhibited amlodipine-induced endothelial intracellular calcium increase. These results suggest that lipid emulsion attenuated the vasodilation induced via amlodipine through inhibiting nitric oxide release in isolated rat aorta, which seems to be mediated via reversal of stimulatory eNOS (Ser1177) phosphorylation and inhibitory eNOS (Thr495) dephosphorylation, which are also induced via amlodipine.

Effects of oxidized soybean oil on the performance of sows and jejunum health of suckling piglets.

Oils provide a considerable amount of energy to the swine diet, but they are prone to lipid oxidation if not properly preserved. Consumption of oxidized oils can adversely affect the animal organism and even the offspring. This study investigated the impact of oxidized soybean oil in the diets of sows from 107 days gestation to 21 days of lactation on the performance of sows and jejunum health of suckling piglets. Sixteen sows were randomly allocated into two groups: one group (n = 8) was fed with the fresh soybean oil (FSO) diet, and another group (n = 8) was treated with the oxidized soybean oil (OSO) diet. Dietary oxidized soybean oil does not affect sow performance. Antioxidant enzyme activity in the milk was reduced significantly in the OSO group, such as the superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and catalase (CAT) activities (p < 0.05). On Day 21, oxidized soybean oil increased tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and interleukin 8 (IL-8) levels in sow milk and the concentrations of TNF-α and IL-8 cytokines in plasma (p < 0.05). Suckling piglets from sows fed on OSO showed a trend towards increased IL-6 and TNF-α in plasma (p < 0.1). The mRNA expression of interleukin 1ß (IL-1ß) was augmented, whereas interleukin 10 (IL-10) was decreased, and zonula occludens-1 (ZO-1) had a tendency to be down-regulated in OSO treatment. This study revealed that the OSO of feed decreased the antioxidant capacity of milk, further contributing to the inflammatory response in the jejunum of suckling piglets.

Effects of soybean oil exposure on the survival, reproduction, biochemical responses, and gut microbiome of the earthworm Eisenia fetida.

With increasing production of kitchen waste, cooking oil gradually enters the soil, where it can negatively affect soil fauna. In this study, we explored the effects of soybean oil on the survival, growth, reproduction, tissue structure, biochemical responses, mRNA expression, and gut microbiome of earthworms (Eisenia fetida). The median lethal concentration of soybean oil was found to be 15.59%. Earthworm growth and reproduction were significantly inhibited following exposure to a sublethal concentration of soybean oil (1/3 LC50, 5.2%). The activity of the antioxidant enzymes total superoxide dismutase (T-SOD), peroxidase (POD), and catalase (CAT) were affected under soybean oil exposure. The glutathione (GSH) content decreased significantly, whereas that of the lipid peroxide malondialdehyde (MDA) increased significantly after soybean oil exposure. mRNA expression levels of the SOD, metallothionein (MT), lysenin and lysozyme were significantly upregulated. The abundance of Bacteroides species, which are related to mineral oil repair, and Muribaculaceae species, which are related to immune regulation, increased within the earthworm intestine. These results indicate that soybean oil waste is toxic to earthworms. Thus, earthworms deployed defense mechanisms involving antioxidant system and gut microbiota for protection against soybean oil exposure-induced stress.

Lipid Compositions of Total Parenteral Nutrition Affect Gut Peyer's Patches and Morphology in Mice.

INTRODUCTION: Although parenteral nutrition (PN) is the only option for providing adequate nutrition to patients who cannot tolerate oral ingestion, it severely impairs intestinal barrier function in terms of morphology and immunity. While addition of either soybean oil (SO) or fish oil (FO) to PN partially reverses these defects, the effects of the oil composition (FO/SO ratio) on morphology and gut-associated lymphoid tissues (GALT) have yet to be elucidated. We focused on the effects of the FO/SO ratio in PN on the number of lymphocytes in Peyer's patches, immunoglobulin A levels, and intestinal structures. METHODS: Male ICR mice (n = 61) were randomized into five groups; oral nutrition (Chow, n = 14) and four groups receiving PN without oral nutrition. PN solutions contained fat emulsions with the following FO:SO ratios: 0:1 (SO, n = 12), 1:11.5 (11.5FSO, n = 17),1:2 (1:2FSO, n = 13) and 1:0 (FO, n = 5). All mice underwent jugular vein catheter insertion. The PN groups were given isocaloric and isonitrogenous nutritional support with 20% of total calories from fat emulsions with equivalent fat delivery in 11.9 g/kg/d. After 5 d of each feeding, Peyer's patches lymphocytes were isolated from the small intestine, counted and analyzed with flowcytometry for determination of their phenotypes (αßTCR+, γδTCR+, CD4+, CD8+ and B cells). Villus height and crypt depth of the jejunum and ileum were evaluated with hematoxylin-eosin staining. Immunoglobulin A levels in the intestinal washings were also determined. RESULTS: Numbers of total lymphocytes and B lymphocytes in PP were increased in the 1:2 FSO-PN but neither in the 1:11.5 FSO nor the FO group, as compared to the SO group. There were no marked differences among the groups in numbers neither of total T cells nor in any of T cell phenotypes determined. The 1:2 FSO group showed significantly greater villus height and crypt depth than the SO group. IgA levels did not differ significantly among the four PN groups. CONCLUSIONS: The PN with 1:2 FSO (FO:SO = 1:2) maintained lymphocyte numbers in PP and intestinal villus morphology at levels nearly the same as those obtained with chow feeding. An appropriate ratio of FO to SO in PN is expected to prevent immunological impairment and morphological atrophy of the gut associated with lack of oral nutrition.

Evaluation of enhancing effect of soybean oil on polymalic acid production by Aureobasidium pullulans HA-4D.

Polymalic acid (PMA) is a water-soluble polyester produced by Aureobasidium pullulans. In this study, the physiological response of A. pullulans after the addition of vegetable oils was investigated. Soybean oil (SBO) is pivotal for shortening fermentation time and achieving high PMA titer. With the addition of 1% (w/v) SBO, the titer and productivity of PMA was, respectively, increased by 34.2% and 80%. SBO acted as a chemical stimulatory agent rather than a carbon source, the enhancement on PMA production was attributed to the component of fatty acid. SBO induced the dimorphism (yeast-like cells and mycelia) of A. pullulans, in vitro enzyme activities indicated that the TCA oxidative branch for malic acid synthesis might be strengthened, which could generate more ATP for PMA synthesis, and the assay of intracellular energy supply validated this deduction. This study provided a new sight for recognizing the regulatory behavior of SBO in A. pullulans.

Lipid metabolic disorders and physiological stress caused by a high-fat diet have lipid source-dependent effects in juvenile black seabream Acanthopagrus schlegelii.

This study was conducted to evaluate the effects of different dietary lipid sources on growth performance, lipid metabolism, and physiological stress responses including oxidative stress (OS) and endoplasmic reticulum stress (ERS) of juvenile Acanthopagrus schlegelii (initial weight 0.88 ± 0.01 g) fed a high-fat diet (HFD). Four isonitrogenous and isolipidic experimental diets containing different lipid sources were formulated: fish oil (FO), palm oil (PO), linseed oil (LO), and soybean oil (SO), respectively. Results indicated that fish fed HFD supplemented with FO significantly improved growth than SO treatment. The high concentrations of aspartate aminotransferase and alanine transaminase were found in HFD supplemented with SO. Fish fed dietary LO supplementation showed significantly lower serum cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein contents than those in SO group. Likewise, hepatic paraffin section analysis indicated that HFD with PO or SO supplementation increased fat drop. The expression levels of peroxisome proliferators-activated receptor alpha (pparα) and silent regulator 1 (sirt1) were significantly elevated by HFD with FO or LO supplementation. Additionally, the key marker of OS malonaldehyde was significantly increased in FO and SO groups. ERS-related genes were activated in dietary PO or SO supplementation and, hence, triggering inflammation and apoptosis by promoting the expression levels of nuclear factor kappa B (nf-κb) and c-Jun N-terminal kinase (jnk). Overall, the present study reveals that lipid metabolic disorders and physiological stress caused by a HFD have significant lipid source-dependent effects, which have important guiding significance for the use of HFD in marine fish.

Proinflammatory State in the Odontogenesis of Fetuses Exposed to Different Types of Fatty Acids during Pregnancy.

OBJECTIVES: The aim of the present study was to analyze the possible changes caused by the maternal ingestion of different types of fatty acids during pregnancy in the proinflammatory state in the odontogenesis of the fetuses. SUBJECT AND METHODS: Twenty-four jaws (n = 6 per group) of Wistar rats were collected on the 20th day of intrauterine life. Mothers were separated on the first day of pregnancy into 4 groups according to diet, as described below: control group (C) - diet with soy oil as a source of fat; saturated fatty acid group (S) - diet with lard in saturated fatty acids; trans-fatty acid group (T) - diet with vegetable fat, rich in trans-saturated fatty acids; and polyunsaturated fatty acid (PUFA) group - diet with fish oil, rich in PUFAs. RESULTS: Microscopic analysis showed no alterations in tissue development of the teeth between the groups with different lipid diets (T, S, and PUFA) when compared to the control group (C); immunohistochemical analysis for the expression of JAK2, STAT3, P-STAT3, SOCS3, and IL-6 showed no statistically significant difference (p > 0.05) compared to the control group. However, there were changes (p < 0.05) between the T group and the PUFA group in the expression of JAK2. CONCLUSION: Thus, lipid consumption in the maternal diet remains a topic to be explored in embryonic development, despite not causing morphological changes to the tooth germ of rats.

Palm Oil-Rich Diet Affects Murine Liver Proteome and S-Palmitoylome.

Palmitic acid (C16:0) is the most abundant saturated fatty acid in animals serving as a substrate in synthesis and ß-oxidation of other lipids, and in the modification of proteins called palmitoylation. The influence of dietary palmitic acid on protein S-palmitoylation remains largely unknown. In this study we performed high-throughput proteomic analyses of a membrane-enriched fraction of murine liver to examine the influence of a palm oil-rich diet (HPD) on S-palmitoylation of proteins. HPD feeding for 4 weeks led to an accumulation of C16:0 and C18:1 fatty acids in livers which disappeared after 12-week feeding, in contrast to an accumulation of C16:0 in peritoneal macrophages. Parallel proteomic studies revealed that HPD feeding induced a sequence of changes of the level and/or S-palmitoylation of diverse liver proteins involved in fatty acid, cholesterol and amino acid metabolism, hemostasis, and neutrophil degranulation. The HPD diet did not lead to liver damage, however, it caused progressing obesity, hypercholesterolemia and hyperglycemia. We conclude that the relatively mild negative impact of such diet on liver functioning can be attributed to a lower bioavailability of palm oil-derived C16:0 vs. that of C18:1 and the efficiency of mechanisms preventing liver injury, possibly including dynamic protein S-palmitoylation.

Suppression of enteroendocrine cell glucagon-like peptide (GLP)-1 release by fat-induced small intestinal ketogenesis: a mechanism targeted by Roux-en-Y gastric bypass surgery but not by preoperative very-low-calorie diet.

OBJECTIVE: Food intake normally stimulates release of satiety and insulin-stimulating intestinal hormones, such as glucagon-like peptide (GLP)-1. This response is blunted in obese insulin resistant subjects, but is rapidly restored following Roux-en-Y gastric bypass (RYGB) surgery. We hypothesised this to be a result of the metabolic changes taking place in the small intestinal mucosa following the anatomical rearrangement after RYGB surgery, and aimed at identifying such mechanisms. DESIGN: Jejunal mucosa biopsies from patients undergoing RYGB surgery were retrieved before and after very-low calorie diet, at time of surgery and 6 months postoperatively. Samples were analysed by global protein expression analysis and Western blotting. Biological functionality of these findings was explored in mice and enteroendocrine cells (EECs) primary mouse jejunal cell cultures. RESULTS: The most prominent change found after RYGB was decreased jejunal expression of the rate-limiting ketogenic enzyme mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (mHMGCS), corroborated by decreased ketone body levels. In mice, prolonged high-fat feeding induced the expression of mHMGCS and functional ketogenesis in jejunum. The effect of ketone bodies on gut peptide secretion in EECs showed a ∼40% inhibition of GLP-1 release compared with baseline. CONCLUSION: Intestinal ketogenesis is induced by high-fat diet and inhibited by RYGB surgery. In cell culture, ketone bodies inhibited GLP-1 release from EECs. Thus, we suggest that this may be a mechanism by which RYGB can remove the inhibitory effect of ketone bodies on EECs, thereby restituting the responsiveness of EECs resulting in increased meal-stimulated levels of GLP-1 after surgery.

Effect of glucose, soya oil and glutamine on protein expression and mammalian target of rapamycin complex 1 pathway of jejunal crypt enterocytes in weaned piglets.

The present study was conducted to evaluate the effects of glucose, soya oil or glutamine on jejunal morphology, protein metabolism and protein expression of the mammalian target of rapamycin complex 1 (mTORC1) signalling pathway in jejunal villus or crypt compartment of piglets. Forty-two 21 d-weaned piglets were randomly allotted to one of the three isoenergetic diets formulated with glucose, soya oil or glutamine for 28 d. On day 14 or 28, the proteins in crypt enterocytes were analysed with isobaric tags for relative and absolute quantification and proteins involved in mTORC1 signalling pathway in villus or crypt compartment cells were determined by Western blotting. Our results showed no significant differences (P > 0·05) in jejunal morphology among the three treatments on day 14 or 28. The differentially expressed proteins mainly took part in a few network pathways, including antimicrobial or inflammatory response, cell death and survival, digestive system development and function and carbohydrate metabolism. On day 14 or 28, there were higher protein expression of eukaryotic initiation factor-4E binding protein-1 in jejunal crypt compartment of piglets supplemented with glucose or glutamine compared with soya oil. On day 28, higher protein expression of phosphor-mTOR in crypt compartment was observed in piglets supplemented with glucose compared with the soya oil. In conclusion, the isoenergetic glucose, soya oil or glutamine did not affect the jejunal morphology of piglets; however, they had different effects on the protein metabolism in crypt compartment. Compared with soya oil, glucose or glutamine may be better energy supplies for enterocytes in jejunal crypt compartment.

Diabetic Rat Hearts Show More Favorable Metabolic Adaptation to Omegaven Containing High Amounts of n3 Fatty Acids Than Intralipid Containing n6 Fatty Acids.

BACKGROUND: While Omegaven, an omega-3 (n3) fatty acid-based lipid emulsion, fosters insulin signaling in healthy hearts, it is unknown whether beneficial metabolic effects occur in insulin-resistant diabetic hearts. METHODS: Diabetic hearts from fructose-fed Sprague-Dawley rats were perfused in the working mode for 90 minutes in the presence of 11 mM glucose and 1.2 mM palmitate bound to albumin, the first 30 minutes without insulin followed by 60 minutes with insulin (50 mU/L). Hearts were randomly allocated to Intralipid (25 and 100 µM), Omegaven (25 and 100 µM), or no emulsion (insulin alone) for 60 minutes. Glycolysis, glycogen synthesis, and glucose oxidation were measured with the radioactive tracers [5-H]glucose and [U-C]glucose. Central carbon metabolites, acyl-coenzyme A species (acyl-CoAs), ketoacids, purines, phosphocreatine, acylcarnitines, and acyl composition of phospholipids were measured with mass spectrometry. RESULTS: Diabetic hearts showed no response to insulin with regard to glycolytic flux, consistent with insulin resistance. Addition of either lipid emulsion did not alter this response but unexpectedly increased glucose oxidation (ratio of treatment/baseline, ie, fold change): no insulin 1.3 (0.3) [mean (standard deviation)], insulin alone 1.4 (0.4), insulin + 25 µM Intralipid 1.8 (0.5), insulin + 100 µM Intralipid 2.2 (0.4), P < .001; no insulin 1.3 (0.3), insulin alone 1.4 (0.4), insulin + 25 µM Omegaven 2.3 (0.5) insulin + 100 µM Omegaven 1.9 (0.4), P < .001. Intralipid treatment led to accumulation of acylcarnitines as a result of the released linoleic acid (C18:2-n6) and enhanced its integration into phospholipids, consistent with incomplete or impaired ß-oxidation necessitating a compensatory increase in glucose oxidation. Accumulation of acylcarnitines was also associated with a higher nicotinamide adenine dinucleotide reduced/oxidized (NADH/NAD) ratio, which inhibited pyruvate dehydrogenase (PDH), and resulted in excess lactate production. In contrast, Omegaven-treated hearts showed no acylcarnitine accumulation, low malonyl-CoA concentrations consistent with activated ß-oxidation, and elevated PDH activity and glucose oxidation, together indicative of a higher metabolic rate possibly by substrate cycling. CONCLUSIONS: Omegaven is the preferred lipid emulsion for insulin-resistant diabetic hearts.

Lipid Emulsion Containing High Amounts of n3 Fatty Acids (Omegaven) as Opposed to n6 Fatty Acids (Intralipid) Preserves Insulin Signaling and Glucose Uptake in Perfused Rat Hearts.

BACKGROUND: It is currently unknown whether acute exposure to n3 fatty acid-containing fish oil-based lipid emulsion Omegaven as opposed to the n6 fatty acid-containing soybean oil-based lipid emulsion Intralipid is more favorable in terms of insulin signaling and glucose uptake in the intact beating heart. METHODS: Sprague-Dawley rat hearts were perfused in the working mode for 90 minutes in the presence of 11 mM glucose and 1.2 mM palmitate bound to albumin, the first 30 minutes without insulin followed by 60 minutes with insulin (50 mU/L). Hearts were randomly allocated to 100 µM Intralipid, 100 µM Omegaven, or no emulsion (insulin treatment alone) for 60 minutes. Glycolysis and glycogen synthesis were measured with the radioactive tracer [5-H]glucose, and glucose uptake was calculated. Phosphorylation of protein phosphatase 2A (PP2A), protein kinase Akt, and phosphofructokinase (PFK)-2 was measured by immunoblotting. Glycolytic metabolites were determined by enzymatic assays. Mass spectrometry was used to establish acylcarnitine profiles. Nuclear factor κB (NFκB) nuclear translocation served as reactive oxygen species (ROS) biosensor. RESULTS: Insulin-mediated glucose uptake was decreased by Intralipid (4.9 ± 0.4 vs 3.7 ± 0.3 µmol/gram dry heart weight [gdw]·min; P = .047) due to both reduced glycolysis and glycogen synthesis. In contrast, Omegaven treatment did not affect insulin-mediated glycolysis or glycogen synthesis and thus preserved glucose uptake (5.1 ± 0.3 vs 4.9 ± 0.4 µmol/gdw·min; P = .94). While Intralipid did not affect PP2A phosphorylation status, Omegaven resulted in significantly enhanced tyrosine phosphorylation and inhibition of PP2A. This was accompanied by increased selective threonine phosphorylation of Akt and the downstream target PFK-2 at S483. PFK-1 activity was increased when compared with Intralipid as measured by the ratio of fructose 1,6-bisphosphate to fructose 6-phosphate (Omegaven 0.60 ± 0.11 versus Intralipid 0.47 ± 0.09; P = .023), consistent with increased formation of fructose 2,6-bisphosphate by PFK2, its main allosteric activator. Omegaven lead to accumulation of acylcarnitines and fostered a prooxidant response as evidenced by NFκB nuclear translocation and activation. CONCLUSIONS: Omegaven as opposed to Intralipid preserves glucose uptake via the PP2A-Akt-PFK pathway in intact beating hearts. n3 fatty acids decelerate ß-oxidation causing accumulation of acylcarnitine species and a prooxidant response, which likely inhibits redox-sensitive PP2A and thus preserves insulin signaling and glucose uptake.

Differential effects of Chinese high-fat dietary habits on lipid metabolism: mechanisms and health implications.

BACKGROUND: The traditional Chinese diet blends lard with vegetable oil, keeping the fatty acid balance intake ratio of saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids at nearly 1:1:1. However, the effects of a mixture of lard and vegetable oil on lipid metabolism have never been researched. In the present study, by simulating Chinese high-fat dietary habits, we explored the effects of a mixture of lard and vegetable oil on lipid metabolism. METHODS: We randomly assigned 50 male C57BL/6 J mice to 5 groups (10 in each group) and fed them lard, sunflower oil (SFO), soybean oil (SBO), lard blended with sunflower oil (L-SFO), or lard blended with soybean oil (L-SBO) for 12 weeks. RESULTS: We found that the final body weights of mice in the lard group were significantly higher than those of mice in the SFO and SBO groups. Body fat rate and volume of fat cell of the lard group were significantly higher than those of the SFO, SBO, and L-SBO groups. Liver triglyceride level of the lard group increased significantly compared to the other groups. Although body fat rate and liver triglyceride level in the SBO and SFO groups decreased compared to those in the other groups, the high-density lipoprotein cholesterol/low-density lipoprotein cholesterol ratio were also significantly decreased in the SBO and SFO groups. CONCLUSIONS: We found that a lard diet induced accumulation of body fat, liver and serum lipids, which can increase the risk of obesity, non-alcoholic fatty acid liver disease, and atherosclerosis. The vegetable oil diet resulted in cholesterol metabolism disorders even though it did not lead to obesity. The mixed oil diet induced body fat accumulation, but did not cause lipid accumulation in the liver and serum. Thus, differential oil/fat diets have an impact on differential aspects in mouse lipid metabolism.

Effect of empiric intravenous intralipid therapy on pregnancy outcome in women with unexplained recurrent implantation failure undergoing intracytoplasmic sperm injection-embryo transfer cycle: a randomized controlled trial.

To evaluate the effect of empiric intralipid infusion therapy on pregnancy outcomes for patients with unexplained recurrent implantation failure (RIF) undergoing intracytoplasmic sperm injection (ICSI). A total of 142 patients with a history of unexplained RIF (3 or more cycles) were included in this randomized controlled trial. Patients were randomized into two groups, study group (n = 71) and control group (n = 71). The study group received intralipid 20% infusion on the day of embryo transfer (ET) and a second dose on the day of pregnancy test. The clinical pregnancy rate in the study group was 36.6% (n = 26) compared to 28.2% (n = 20) in the control group (OR 1.47, CI 0.72-2.98, p = .282). The live birth rate in the study group was 18.3% (n = 13) and 14.1% (n = 10) in the control group (OR 1.37, CI 0.55-3.36, p=.49). No side effects of intralipid therapy were reported in the study period. There was improvement in the pregnancy rate among women with unexplained RIF who received empiric intralipid infusion therapy; however, this improvement did not reach statistical significance.

Structure of intermediate filament assembly in hair deduced from hydration studies using small-angle neutron scattering.

Intermediate filaments (IFs) are ubiquitous in biological structures including hair. Small-angle neutron scattering (SANS) data from hydrated samples were used in this study to investigate the distribution of water in hair, and model the structure of the IF assembly. A main diffraction peak at a d-spacing of ∼90 Å, and two weaker reflections show that IFs are arranged in a ∼105 Šquasi-hexagonal lattice. Changes in the diffraction peaks show that only a small fraction of the water absorbed by hair enters between the IFs, and little water diffuses into the core of the IFs. The amount of water in the IF assembly increases rapidly up to 10% relative humidity (RH), and then slowly with further increase in RH. Most of the water appears to reside outside the IF assembly, in the voids and at the interfaces, and contribute to the central diffuse scattering. The IF assembly in the decuticled hair absorbs more water and is more ordered than that the native hair. This suggests that cuticle acts as a barrier, and might constrain the structure by compressing the cortex radially. Treatments with oils that are hydrophobic, heat treatment, and reduction of the S-S linkages that opens up the matrix by disulfide bond cleavage, all affect structure and water permeability. Coconut oil was found to impede hydration more than the soybean oil because of its ability to penetrate deeper into hair. A new model for the IF assembly that is sterically more favorable than the previous models is proposed.

Disparate Candida albicans Biofilm Formation in Clinical Lipid Emulsions Due to Capric Acid-Mediated Inhibition.

Receipt of parenteral nutrition (PN) remains an independent risk factor for developing catheter-related bloodstream infections (CR-BSI) caused by fungi, including by the polymorphic fungus Candida albicans, which is notoriously adept at forming drug-resistant biofilm structures. Among a variety of macronutrients, PN solutions contain lipid emulsions to supply daily essential fats and are often delivered via central venous catheters (CVCs). Therefore, using an in vitro biofilm model system, we sought to determine whether various clinical lipid emulsions differentially impacted biofilm growth in C. albicans We observed that the lipid emulsions Intralipid and Omegaven both stimulated C. albicans biofilm formation during growth in minimal medium or a macronutrient PN solution. Conversely, Smoflipid inhibited C. albicans biofilm formation by approximately 50%. Follow-up studies revealed that while Smoflipid did not impair C. albicans growth, it did significantly inhibit hypha formation and hyphal elongation. Moreover, growth inhibition could be recapitulated in Intralipid when supplemented with capric acid-a fatty acid present in Smoflipid but absent in Intralipid. Capric acid was also found to dose dependently inhibit C. albicans biofilm formation in PN solutions. This is the first study to directly compare different clinical lipid emulsions for their capacity to affect C. albicans biofilm growth. Results derived from this study necessitate further research regarding different lipid emulsions and rates of fungus-associated CR-BSIs.

Lipids and insulin regulate mitochondrial-derived peptide (MOTS-c) in PCOS and healthy subjects.

OBJECTIVE: Polycystic ovarian syndrome (PCOS) is a heterogeneous endocrine disorder associated with mitochondrial dysfunction and insulin resistance (IR). MOTS-c, a mitochondrial peptide, promotes insulin sensitivity (IS) through activating AKT and AMPK-dependent pathways. The current study was designed to examine the response of MOTS-c to lipids (intralipid) followed by insulin in PCOS and healthy subjects. METHODS: All subjects underwent 5-hour intralipid/saline infusion with a hyperinsulinemic-euglycaemic clamp in the final 2 hours. Plasma samples were collected to measure circulating MOTS-c using a commercial ELISA kit. Subsequently, this was repeated following an eight-week exercise intervention. RESULTS: Intralipid significantly increased plasma MOTS-c both in controls and PCOS subjects, whilst the insulin infusion blunted the intralipid-induced response seen for both lipids and MOT-c. Intralipid elevated plasma MOTS-c to 232 ± 124% of basal in control (P < 0.01) and to 349 ± 206% of basal in PCOS (P < 0.001) subjects. Administration of insulin suppressed intralipid-induced MOTS-c from 232 ± 124% to 165 ± 97% (NS) in control and from 349 ± 206% to 183 ± 177% (P < 0.05) in PCOS subjects, respectively. Following exercise, intralipid elevated plasma MOTS-c to 305 ± 153% of basal in control (P < 0.01) and to 215 ± 103% of basal in PCOS (P < 0.01) subjects; insulin suppressed intralipid-induced MOTS-c only in controls. CONCLUSIONS: In conclusion, this is the first study to show increased lipid enhanced circulating MOTS-c whilst insulin attenuated the MOTS-c response in human. Further, eight weeks of moderate exercise training did not show any changes in circulating MOTS-c levels in healthy controls and in women with PCOS.

Mixed Lipid, Fish Oil, and Soybean Oil Parenteral Lipids Impact Cholestasis, Hepatic Phytosterol, and Lipid Composition.

OBJECTIVES: In parenteral nutrition-dependent infants and children, intestinal failure (IF)-associated liver disease (IFALD) remains an important problem. A comparative study was undertaken of parenteral mixed lipid (ML), ω-3 predominant fish oil (FO), and ω-6 predominant soybean oil (SO) emulsions in regards to hepatic phytosterol, neutral lipid, fatty acid (FA) content, and the relationship to cholestasis in piglets. METHODS: Neonatal piglets received parenteral nutrition, varying in lipid dose (5 or 10 g·â€Škg ·â€Šday) and formulation: SO5 (n = 5), SO10 (n = 5), FO5 (n = 5), and ML10 (n = 5). On day 14, liver chemistry, bile flow, histology and neutral lipid staining were assessed. Hepatic triglyceride FA content was determined using thin layer and gas chromatography, and phytosterol content was assessed using gas chromatography-mass spectrometry. RESULTS: SO groups had higher prevalence of biochemical cholestasis (P < 0.04) and lower bile flow (P < 0.0001). Hepatic campesterol, stigmasterol, and ß-sitosterol were highest in SO10 (P < 0.0001). Hepatic FA (P < 0.03) and ω-6/ω-3 FA ratio (P < 0.0001) were higher in the SO groups. Neutral lipid accumulation (P = 0.3) and liver histology (P = 0.16) were not different between groups. Univariate predictors of bile flow were: campesterol (r = -0.77, P = 0.001), ß-sitosterol (r = -0.74, P = 0.002), stigmasterol (r = -0.74, P = 0.002), ω-6 FA (r = -0.72, P = 0.002), and ω-3 FA (r = 0.59, P = 0.02). Only campesterol independently predicted bile flow. CONCLUSIONS: ML and FO lipid emulsions reduce cholestasis in association with lowered hepatic phytosterol and lipid content. Lower hepatic phytosterol and ω-6 FA content, and higher ω-3 FA content are hepatoprotective. Multivariate analysis suggests reduced phytosterol accumulation may best explain the hepatoprotective effect of fish oil-containing lipids.